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    FAO Nutrition Meetings
    Report Series No. 40A,B,C
    WHO/Food Add./67.29




    TOXICOLOGICAL EVALUATION OF SOME
    ANTIMICROBIALS, ANTIOXIDANTS, EMULSIFIERS,
    STABILIZERS, FLOUR-TREATMENT AGENTS, ACIDS AND BASES





    The content of this document is the result of the deliberations of the
    Joint FAO/WHO Expert Committee on Food Additives which met at Rome,
    13-20 December, 19651 Geneva, 11-18 October, 19662




                   

    1 Ninth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series, 1966 No. 40; 
    Wld Hlth Org. techn. Rep. Ser., 1966, 339

    2 Tenth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series, 1967, in press; 


    Food and Agriculture Organization of the United Nations
    World Health Organization
    1967


    ACETIC ACID AND FATTY ACID ESTERS OF GLYCEROL

    Synonyms                     Acetylated mono-and diglycerides; Acetic
                                 acid esters of mono-and diglycerides;
                                 Acetoglycerides; Acetofats

    Chemical description         The product consists of mixed glycerol
                                 esters of acetic acid and fatty acids.

    Structural formula

                                 CH2 - OR
                                 CH - OR'
                                 CH2 - OR"

                                 Where R, R' and R" represents the fatty
                                 acid or acetic moiety and R or R' will
                                 be hydrogen in the case of the mono- or
                                 di-esters.

    Definition                   Acetylated mono- and diglycerides
                                 contain mono- and some di-esters of
                                 fatty acids with glycerol which is
                                 itself partially acetylated. The product
                                 may contain free glycerol and free fatty
                                 acids.

    Description                  Acetylated monoglycerides vary in
                                 consistency from liquids to solids and
                                 are white to pale yellow in colour. They
                                 may have an acetic acid odour.

    Uses                         As emulsifier.

    Biological Data

    Biochemical aspects

         The long-chain fatty acids in triglycerides may be replaced with
    one or more acetic acid groups to produce mono- or diacetins
    (acetoglycerides) which are resistant to changes in consistency, heat
    damage and oxidative rancidity (Alfin-Slater et al., 1958; Ambrose &
    Robbins, 1956b). Lipolytic studies in rats showed the presence of
    large amounts of free fatty acids but only traces of free acetic acid
    in the lipids isolated from the stomach after feeding acetoglycerides.
    Ligation of the pylorus indicated a more rapid absorption or the
    acetic acid moiety by the stomach wall than of glycerol and monoacetin
    (Hertnig et al., 1956). Absorption of acetoolein or acetostearin,
    given as 20 per cent. of the diet, was studied in groups of 10 adult
    male rats. Acetooleins were better absorbed than acetostearins. Faecal
    lipid estimations showed much greater absorption (i.e. lowest

    excretion) in rats of unsaturated acetoglycerides (acetooleins) than
    of saturated acetoglycerides (acetostearins) (Ambrose & Robbins,
    1956b).

         The digestibility coefficients of acetoglycerides fed as 20 per
    cent. of the diet to rats varied between 94 and 99 per cent. depending
    on the composition of the mixture administered (Ambrose & Robbins,
    1956b). In another study, groups of 10 male weanling rats were fed
    diets containing 0 or 30 per cent. of 2 different acetostearins for 20
    weeks. Tissue cholesterol levels (plasma, liver, adrenal) for the 30
    per cent. level were similar to those in rats on a fat-free calorie
    restricted diet (Coleman et al., 1963).

    Acute toxicity

                                                                     

    Animal     Route      LD50              Reference
                          (mg/kg 
                          body-weight)
                                                                     

    Rat        oral       4 000             Ambrose & Robbins, 1956a
                                                                     

         No toxic symptoms were seen in rats after single doses of 4000
    mg/kg body-weight of acetostearin or acetoolein. Daily i.v. injection
    of 80-100 mg acetostearin into rabbits for 15 days caused no apparent
    ill effects and viscera showed no pathological charges. Acetostearin
    cleared completely from the blood plasma within 15-30 minutes (Ambrose
    & Robbins, 1956a; Alfin-Slater et al., 1958),

    Short-term studies

         Rat. Groups of 10 male weanling rats received diets containing
    25 per cent. of either stearin, olein, diacetostearin or diacetoolein,
    and additional groups received 50 per cent. olein or diacetoolein for
    8 weeks or 15 per cent. acetoolein for 12 weeks. There was no
    difference between test and control groups with regard to body-weight
    gain, food consumption or food efficiency, except for the groups
    receiving stearins. Only in the groups receiving diacetostearin was
    the coefficient of utilization markedly higher. Results of examination
    of blood and urine were normal (Mattson et al,, 1956). Studies for 7
    months on groups of 5 male and 10 female rats using 10 per cent.
    acetostearin in the diet with additional supplements of Vitamin E
    showed improved reproduction performance (as measured by litter
    numbers and pups per litter in four successive ratings) compared with
    controls or animals on acetostearin alone (Ambrose et al., 1958b).

    Long-term studies

         Rat. Six groups of 5 weanling male rats each were fed diets
    containing O, 0.25, 0.5, 1, 2 and 4 per cent. acetostearin, and
    another 4 groups of rats ware fed diets containing 0, 0.25, 0.5 and
    1.0 per cent. acetoolein for 57 weeks. Body-weight gain, food intake
    and mortality did not differ from those of the controls. Measurement
    of relative weights of major organs revealed decreased testicular
    weights at all levels of acetoolein and with the 0.25 and 0.5 per
    cent. levels of acetostearin. Microscopic examination showed no
    difference from controls except for testicular hypoplasia and
    suppression of spermatogenesis of a variable degree in all test groups
    (Ambrose & Robbins, 1956a).

         In another experiment, 3 acetostearins and 2 acetooleins were fed
    to groups of 10 male and 10 female rats each at 0, 5, 10 and 20 per
    cent. of their diet. Parental generation animals on 20 per cent.
    acetoglyceride were sacrificed after 57 weeks, 86 weeks and 101 weeks.
    Mortality rate was not increased at any dose level up to 57 weeks, but
    some increase occurred in all test groups compared with controls after
    86 weeks. Body-weight gain was slightly depressed at the 20 per cent.
    level. Examination of major organs showed consistently reduced
    testicular weight at the 20 per cent. level of all three acetostearins
    and at the 5 per cent. and 10 per cent. levels of two acetostearins.
    Significant liver enlargement was also observed at the 20 per cent
    level of acetostearins but liver glycogen was unaffected. Food
    utilization was decreased by acetostearin more than by acetoolein
    depending on dose. A variety of pathological changes ware observed
    with individual acetoglycerides at varying dietary levels, but these
    changes were attributed to imbalance of the test diet with respect to
    Vitamin E and essential fatty acids. Fatty tissue changes reminiscent
    of sclerema adiposum neonatorum (foci of foreign body reactions)
    especially near the gut were seen with all acetostearins at 20 per
    cent. level but none in the other groups (Ambrose et al., 1956a).

    Comments

         Acetoglycerides are readily hydrolysed in the gastrointestinal
    tract and dealt with in the body in a manner similar to other
    glycerides. The digestibility studies are only of limited value since
    the inclusion of materials of this sort in an adequate quantity of
    lipid fat, occurring naturally in the diet, ensures satisfactory
    absorption. Dietary loads of a food additive in excess of 10 per cent.
    are of little value in the assessment of safety-in-use as many
    irrelevant effects may occur, such as observed with high-dose levels
    of acetostearin. (E.g. testicular atrophy due to an increased
    requirement for Vitamin E, and foreign body reaction in adipose tissue
    due to overloading with saturated fatty acids.) Such effects are very
    likely to be irrelevant considering the levels of use of these
    compounds. Evaluation is based on the biochemical and metabolic
    studies because the breakdown products are normal dietary
    constituents.

    Evaluation

    Estimate of acceptable daily intake for man

    See mixed tartaric and acetic and fatty acid esters of glycerol 
    (p. 96)

    REFERENCES

    Ambrose, A. M. & Robbins, D. J. (1956a) J. Amer. Pharm. Ass. Sci.
    Ed., 45, 482

    Ambrose, A. M. & Robbins, D. J. (1956b) J. Nutr., 58, 113

    Ambrose, A. M., Robbins, D. J. & Cox, A. J. jr (1958a) Food Res.,
    23, 536

    Ambrose, A. M., Robbins, D. J. & De Eds, F. (1958b) Food Res., 23,
    550

    Alfin-Slater, R. B., Coleman, R. D., FeŁge, R. 0. & Altschul, A. M.
    (1958) J. Amer. Oil Chem. Soc., 35, 122

    Coleman, R. D., Gayle, L. A. & Alfin-Slater, R. B. (1963) J. Amer.
    Oil Chem. Soc., 40, 737

    Hertnig, D. C., Ames, S. R., Embree, N. D. & Harris, P. L. (1956)
    Fed. Proc., 15, 556

    Mattson, F. H., Alexander, J. C., Baur, F. J. & Reller, H. H. (1956)
    J. Nutr., 59, 277
    


    See Also:
       Toxicological Abbreviations